CN107106149A - Fine needle elastogram device and system for the measurement of material property - Google Patents

Abstract

In an aspect, elastogram system includes elastogram device and is connected to the position sensing apparatus of the elastogram device.The elastogram device includes shell, is detachably attached to the detecting element of the shell, and the force snesor being attached in the shell, wherein the force snesor is connected to the detecting element.In another aspect, elastograph imaging method is included：By in detecting element insertion material；The signal for the power for indicating to be applied to the detecting element when the detecting element is inserted in the material is produced by the force snesor for the base for being connected to the detecting element；And based on the signal, obtain the mapping of the spatial variations of material property in the material.

Description

Fine needle elastogram device and system for the measurement of material property

The cross reference of related application case

This application claims the entitled " FINE that Jim Chu Siji (Gimzewski) et al. was submitted on the 11st in August in 2014 NEEDLE ELASTOGRAPHY DEVICE AND SYSTEM FOR THE MEASUREMENT OF MATERIAL PROPERTIES (the fine needle elastogram device and system for being used for the measurement of material property) " U.S. provisional patent application cases 62/035,976 rights and interests, the content of this application case is incorporated by reference herein in its entirety.

Background technology

Expect the new method of identification early-stage cancer.

For example, thyroid cancer is a kind of cancer most easily cured.Thyroid cancer is most common endocrine cancer, occupies annual The 1.0% to 1.5% of all new cancers made a definite diagnosis in the U.S..It is largely because shortage understanding and delayed diagnosis, only 2013 Year in the U.S., thyroid cancer influence about 60 and causes about 1 at 220 people, and 850 people are dead, wherein 60% case is being difficult to treat The mid-term of cancer or excessive risk phase make a definite diagnosis.

In another example, the main cause of cancer mortality is breast cancer in the U.S. most common a kind of cancer and women. In Pre-menopausal Women, confirm that 1/12nd in lump is pernicious.In postmenopausal women, about two in confirmation lump/ One is pernicious.Accordingly, it would be desirable to effective assessment and timely diagnose exclude malignant tumour and make unnecessary test and Invasive surgery is minimized, and it also requires minimizing universal excessive diagnosis and the over-treatment of breast cancer.Breast cancer is generally used The three-stage process of clinical breast examination, imaging and tissue sampling is diagnosed.However, palpable breast lump be it is common and And be in generally benign (for example, fibrous tumours and tumour), therefore in the clinical breast examination stage, there is excessively examining of meriting attention It is disconnected.

In addition to palpation, FNA (FNA) cytology (FNAC) can be used, and FNAC is to be used at present in the U.S. In the most accurate and most sensitive diagnostic tool of preliminary screening patient.However, FNAC have with specimen quality, Sampling techniques, hold Row suction doctor technology, understand extract virologist experience and benign between pernicious Follicular tumor The relevant defect of overlapping cytologic characteristic.For example, thyroid gland FNA FNAC sensitivity and specificity values are respectively 65% to 98% Between and 73% to 100% between change.The major reason of the Sensitivity and Specificity of such wide scope is cell pathology How the species and cytopathologist how family handles " suspicious " define false positive and false negative result.In addition, FNAC points Analysis is related to sample preparation and imaging capability, and is limited in terms of quantitative judge malignant tumour.

In recent years, elastograph imaging method has been used to determine different structure and its relation respective between tissue elasticity, this It can aid in diagnosing malignant tumor.Elastogram provides the method for qualitatively image tissue rigidity, and can provide Extra improved sensitiveness, objectivity or such as rigidity pattern details (for example, with hand touch or FNAC compared with).However, bullet Property imaging be expensive and qualitatively, and be related to the instrument and operative skill of specialty.

Therefore, the unmet demand to quantitative, cost efficient and wieldy early-stage cancer diagnostic method is still suffered from. In this context, it is necessary to develop embodiment described herein.

Disclosure

In an aspect, elastogram system is comprising elastogram device and is connected to the elastogram device Position sensing apparatus.Elastogram device is included：Shell；Detecting element, it is detachably attached to the shell；And power is passed Sensor, it is attached in the shell, and the force snesor is connected to the detecting element.

In another aspect, elastogram system is included：Shell；Pin, it is detachably attached to the shell；And power Sensor, it is located in the shell and is fixedly mounted relative to the pin, wherein force snesor detection is applied to institute State the power of pin.

In another aspect, elastograph imaging method is included：By in detecting element insertion material；By being connected to the detection member The force snesor of the base of part produces the signal for the power for indicating to be applied to the detecting element by the material；And based on described Signal obtains the mapping of the spatial variations of the material property in the material.

Brief description of the drawings

Fig. 1 is the diagram of the example of fine needle elastogram (FNE) system in accordance with an embodiment of the present disclosure.

Fig. 2 is the diagram of the example of computing device in accordance with an embodiment of the present disclosure.

Fig. 3 A are the diagrams of the example of fine needle elastogram (FNE) device in accordance with an embodiment of the present disclosure.

Fig. 3 B are the expressions of the FNE devices of Fig. 3 A in accordance with an embodiment of the present disclosure.

Fig. 3 C are the diagrams for the FNE devices for holding Fig. 3 A.

Fig. 4 is the expression of the FNE devices of Fig. 3 A in accordance with an embodiment of the present disclosure.

Fig. 5 is the electric charge and the curve map of power of FNE devices in accordance with an embodiment of the present disclosure.

Fig. 6 is the curve map of power during the insertion of FNE devices in accordance with an embodiment of the present disclosure and distance.

Fig. 7 A are the changes of the power during the insertion of FNE devices and the curve map of distance in accordance with an embodiment of the present disclosure.

Fig. 7 B are the bar charts of the power inhomogeneities of the curve in the curve map for represent Fig. 7 A.

Fig. 7 C are the derivative and the curve of distance of the power during the insertion of FNE devices in accordance with an embodiment of the present disclosure Figure.

Fig. 7 D are the bar charts of the rigidity inhomogeneities of the curve in the curve map for represent Fig. 7 C.

Fig. 8 A are the diagrams in FNE devices insertion neck phantom in accordance with an embodiment of the present disclosure.

Fig. 8 B are the ultrasonoscopys during FNE devices insert neck phantom in accordance with an embodiment of the present disclosure.

Fig. 9 A are the curve maps of power during the insertion of FNE devices in accordance with an embodiment of the present disclosure and distance.

Fig. 9 B are the ultrasonoscopys of a part for neck phantom.

Figure 10 A are the curve maps of power during the insertion of FNE devices in accordance with an embodiment of the present disclosure and distance.

Figure 10 B are the ultrasonoscopys of a part for neck phantom.

Figure 11 is the change of the power during the insertion of FNE devices and the curve of distance change in accordance with an embodiment of the present disclosure Figure.

Figure 12 A are the changes of the power during the insertion of FNE devices and the curve map of distance in accordance with an embodiment of the present disclosure.

Figure 12 B are the bar charts of the power inhomogeneities of the curve in the curve map for represent Figure 12 A.

Figure 12 C are the derivative and distance change of the power during the insertion of FNE devices in accordance with an embodiment of the present disclosure Curve map.

Figure 12 D are the bar charts of the rigidity inhomogeneities of the curve in the curve map for represent Figure 12 C.

Figure 13 A are the diagrams of the example of FNE devices in accordance with an embodiment of the present disclosure.

Figure 13 B are that the block diagram of Figure 13 A FNE devices is represented.

Figure 14 A are schematically showing for a part for Figure 13 A FNE devices.

Figure 14 B are the images of the prototype of the charge amplifier of Figure 13 A FNE devices.

Figure 15 is the curve map of the power and pin depth during the insertion of FNE devices in accordance with an embodiment of the present disclosure.

The diagram of the technology in vivo mapped for the scrambling that Figure 16 is performed in breast tissue.

Embodiment

It is first that acronym, abbreviation and the symbol used in the disclosure is included in those shown in three row of table 1 Letter abbreviations, abbreviation and symbol.

Table 1

Different materials have dissimilar material properties, and the investigation of the material property of material is provided on material type Information.Relative to biomaterial, the information on biomaterial type is provided the investigation of the material property of biomaterial.Example Such as, the scrambling such as cancer, tumour and lipoma can be detected by checking biomaterial characteristic.In addition, biological The investigation of material can be used to confirm that in the absence of scrambling.

In the disclosure, for the sake of simplicity, term " tissue " is used to represent " biomaterial "；It should be understood, however, that " biological material Other materials beyond material " cover tissue.In addition, the concept of the application extends to non-biological material.

One classification of material property is resistance.As described in this disclosure, by inserting a needle into tissue and quantifying The resistance that measurement pin is subjected to, pin can be used for detecting resistance.The example of resistance in tissue is recovered comprising inertia force, elasticity Power, frictional force and cutting force.The resistance measured will allow mapping scrambling and capture in scrambling and on its side The organization material characteristic changed at boundary.For example, the accurate mapping of scrambling allows more accurately diagnosing and controlling for scrambling Treat or remove (for example, excision).

As described in this disclosure, FNE devices, FNE systems and FNE technologies are used for the resistance for measuring tissue.FNE device bags Containing force snesor and pin.In one or more embodiments, force snesor is mounted in the piezoelectricity between pin and its mounting seat Crystal.Such device can be used in carrying out mapping table with the resolution ratio and paracentesis depth more than the existing apparatus comprising medical ultrasonic The change of material property under face.Improved resolution ratio improves speed and the degree of accuracy of diagnosis.Therefore, disclosed FNE devices, System and technology can substitute the medical ultrasonic in multiple clinical practices.In addition, too high or unavailable in miscellaneous equipment cost When, or when that can not use technical staff or virologist, disclosed FNE devices, system and technology is particularly useful.

Fig. 1 illustrates the example of the FNE systems 100 according to one or more other embodiments of the present disclosure.System 100 includes FNE Device 110, the FNE devices include detecting element 120, force snesor 130 and optional outer cover unit 140 again.FNE systems 100 Position sensing apparatus 150, sensor interface 160 and processing unit 170 are alternatively further included, one or more can To be comprised in outer cover unit 140, or can be outside outer cover unit 140.

Detecting element 120 be high-aspect-ratio (high aspect ratio) detecting element (for example, about two or more, about 3 or It is bigger, about 4 or bigger or about 5 or bigger and be up to about 10 or bigger, or up to about 20 or bigger depth-width ratio (aspect ratio)).The example of detecting element 120 includes pin, pipe or line, such as FNAC biopsies hypodermic needle, determining according to capillary Pin processed, customization solid needle, nano wire and nanotube etc..

Force snesor 130 is connected to detecting element 120.The example of force snesor 130 includes piezo-electric crystal, strain gauge and tool The rigidity for having displacement measurement sensor (for example, capacitance displacement sensor, optical displacement sensor or inductance displacement sensor) is scratched Bent element.

Outer cover unit 140 is optional and comprising attachment area or closed area, detecting element 120 and force snesor 130 can dispose or be installed to the attachment area or be mounted or installed in the closed area.Implement one or more In example, detecting element 120 and force snesor 130 can be mounted to have fixed spatial relationship or distance relative to another one, and And there is fixed spatial relationship or distance, this speed for contributing to information processing and the degree of accuracy relative to outer cover unit 140.One In individual or multiple embodiments, outer cover unit 140 is embodied as single component.In one or more embodiments, outer cover unit 140 is real Apply as multiple components, for example, head portion and holder part.In such embodiment, for example, force snesor 130 and detection Element 120 can be mounted in head portion, and force snesor 130 and detecting element 120 one or two can Releasably install.Then, head portion can be positioned in holder.Such shell with head portion and holder part Unit 140 is provided for hand-held (for example, referring to Fig. 3 C).

In one or more embodiments, FNE devices 110 are implemented in modularization framework, and this allows to remove detecting element 120 and can allow remove force snesor 130.For example, such embodiment provides detecting element 120 or force snesor 130 Sterilization is replaced.Thus, for example, the pin produced in enormous quantities may be used as detecting element 120, thus reduce cost and improve and defend It is raw.In addition, the ability for replacing force snesor 130 is provided for upgrading force snesor 130, or by a type of force snesor 130 change over another type of force snesor 130, for particular survey.

Position sensing apparatus 150 is optional, and senses or set up the displacement of absolute position, relative position or position. Position can refer to coordinate in three-dimensional (3D) space and relative to line or the orientation of plane.For example, can according to definitely or The change of relative position, or combine speed and/or acceleration to determine displacement by position.The example of position sensing device 150 Comprising gyroscope, accelerometer, Inertial Measurement Unit, ultrasound displacement sensor, magnetic displacement transducer, electric displacement sensor or its One in its sensor or combination.Position sensing apparatus 150 can for example be embodied as position for setting up detecting element or The code level in path.

Sensor interface 160 is optional, and collects information to provide sensor information from position sensing apparatus 150 To another component, such as processing unit 170.Sensor interface 160 can include analog or digital component, or its combination.For The wherein embodiment of the output digital data of position sensing apparatus 150, sensor interface 160 includes digital interface.For its middle position The embodiment that sensing device further 150 exports analogue data is put, sensor interface 160 includes analog interface.Analog interface can be included Analog-digital converter (ADC)；However, must be not necessarily such case.Sensor interface 160 can receive information with other components Form provide arrive other components.If for example, the analog input end of processing unit 170 is provided information into, by sensor The form that interface 160 is exported can be simulation；But if the digital input end of processing unit 170 is provided information into, then The form exported by sensor interface 160 can be digital.These examples are nonrestrictive, because processing unit 170 Digital input end can be couple to analog signal (for example, detecting when signal spans threshold value), and the mould of processing unit 170 The signal of digital form can be received (if for example, limitation to be applied by the response time of analog input end by intending input Interior frequency provides data signal).In one or more embodiments, sensor interface 160 connects comprising serial or parallel data Mouthful, provide information by the serial or parallel data-interface according to special or industry agreement.In one or more embodiments, Sensor interface 160 includes one or more of hardware or software wave filter, for example, low pass, high pass or bandpass filter, product Divide device or other smoothing filters, decimation filter, tuningout wave filter etc..

Processing unit 170 is optional, and is the calculating from the receive information of sensor interface 160 and processing described information Device.In one or more embodiments, information is all handled with identification material type and establishment in processing unit 170 The mapping of scrambling.In other embodiments, information carries out part processing and by processing unit in processing unit 170 170 are provided to another computing device (not shown), for further processing.For example, processing unit 170 can be according to from sensor The information that interface 160 is received determines material property, and provides material property to another computing device in outside, for knowing Other material type and mapping.

Processing unit 170 can further control position sensing apparatus 150, for example, sensed with opening or closing the position Device, setting sensor parameter or offer alignment settings.

Fig. 2 illustrates the example (for example, processing unit 170) of general computing device.Computing device 200 comprising processor 210, Memory 220, input/output interface 230 and communication interface 240.Bus 250 provides two in the component of computing device 200 Or more between communication path.Shown component provides and is nonrestrictive by way of illustration.Computing device 200 can be with With extra or less component, or multiple same components.

Processor 210 represents general processor, digital signal processor, microprocessor, microcontroller, application specific integrated circuit (ASIC), field programmable gate array (FPGA), realize other circuits of processor function or together with associated logic and interface One or more of its combination of circuit.

Memory 220 is represented in volatibility and nonvolatile memory for storage information (for example, instruction and data) One or two.The example of memory comprising semiconductor memory system (for example, EPROM, EEPROM, flash memories, RAM or ROM device), magnetic medium is (for example, built-in hard disk or moveable magnetic disc or tape, magneto-optic disk, CD-ROM and DVD-ROM Disk, holographic disk etc.).

The part of FEN systems 100 may be embodied as being performed by processor 210 in the memory 220 of computing device 200 Computer-readable instruction.

Input/output interface 230 represents common and provided from interface of the intraware of computing device 200 to external module Electric component and optional code.Example includes the driver IC with associated programming, or connecing to external memory storage Mouthful.

Communication interface 240 represents common and provided from the electric of interface of the intraware of computing device 200 to external network Component and optional code, the external network for example, processor 210 provided by the information outside FNE systems 100 net Network.Communication interface 240 can be two-way so that for example data can be sent from computing device 200, and instruction and renewal can To be received by computing device 200.

Bus 250 represents one or more interfaces between the component in computing device 200.For example, bus 250 can be wrapped A number of other components containing the special connection between processor 210 and memory 220, and processor 210 and computing device 200 Between shared connection

Embodiment of the disclosure is related to a kind of non-transitory computer-readable storage media (for example, memory 220), thereon With the computer code for performing various computer-implemented operations.Term " computer-readable storage used herein Medium " includes and can store or encode for performing operate as described herein, the instruction of methods and techniques or computer code Sequence any medium.Medium and computer code can specially design and be configured to embodiment of the disclosure purpose Those media and computer code, or the medium and computer code can be technical staff in computer software fields Know with it is available.

The example of computer code includes the machine code that is for example produced by compiler, and containing being used by computer The file for the high level code that interpreter or compiler are performed.For example, embodiment of the disclosure can use Java, C++, or its The programming language and developing instrument of its object-oriented is implemented.The additional examples of computer code include encrypted code and compression generation Code.In addition, embodiment of the disclosure can be downloaded as computer program product, the computer program product can be via biography Defeated channel is delivered to requesting computer (for example, client computer or difference from remote computer (for example, server computer) Server computer).Another embodiment of the present disclosure can be replaced or with reference to machine executable software instruction in hard-wired circuitry It is middle to implement.

FNE systems 100 allow the quantitative change that material property is mapped when by the insertion material of detecting element 120.One In individual or multiple embodiments, detecting element 120 is inserted into patient's body (for example, human patientses or other animal patients), life Thing tissue or the other materials obtained from patient, or in other materials.In one or more embodiments, the energy of force snesor 130 It is enough to be installed relative to detecting element 120 so that force snesor 130 is partly or entirely kept during the insertion of detecting element 120 In patient-external.In one or more embodiments, FNE systems 100 obtain the one or more material properties or volume of material Spatial variations mapping.In one or more embodiments, based on the mapping, FNE systems 100 obtain for example by cancer or The instruction of the possibility of material scrambling caused by Other diseases.In the case of cancer, in one or more embodiments, FNE systems 100 can also obtain the classification or instruction by stages of cancer.

Described in overview after FNE systems 100, next some examples are provided.The example below describes the one of the disclosure The particular aspects of a little embodiments, to illustrate to those skilled in the art and provide description.The example is not necessarily to be construed as limitation The disclosure, because example, which is only provided, helps to understand and put into practice the ad hoc approach of some embodiments of the present disclosure.

Example 1

For the FNE devices for the localized variation that mechanics tissue characteristics are determined in biomethanics

Example 1 describes FNE devices, system and the technology for assessing thyroid nodule.Health tissues and pathological tissues it Between stiffness difference it is relatively common in thyroid cancer, and generally initially investigated by palpation.In 4% to 7% population Middle to find palpable thyroid nodule, wherein thyroid cancer accounts for the 5% to 10% of these tubercles.

Health and pathological tissues show different mechanical characteristics, and therefore, mechanics (mechanical) characteristic of tissue has Clinical diagnosis meaning.The design and exploitation of FNE device of the report of example 1 with integrated FNAC pins, it is described after pin insertion FNE devices allow the localized variation based on elastic force, frictional force and cutting force to carry out quantitative and sensitive assessment to tissue and material.Peace Piezoelectric force transducer mounted in the base position of FNA pins resists the power of pin puncture with the resolution measurement of μm level.

The measurement accuracy (± 5 μm) and axle of prototype FNE devices are tested using the gelatin substrate and raw pears of control mm sizes To resolution ratio (about 20 μm), to assess the optimization of pin puncture resistance, power inhomogeneities and pin puncture speed.Gelatin and pears, which have, to be divided The not other sensation similar with tumor tissues with health tissues.

FNE is demonstrated in the quantitative of the thyroid tumors tubercle of simulation also in ultrasonic neck phantom, biomethanics difference Device, wherein fluidity and solid nodules are detected, coupled with ultrasonic guidance in a model.With fluidity tubercle or corresponding to ultrasound The region of healthy parathyroid tissue in model is compared, and data substantially show the higher force change in solid nodules.For example, relative In one dimension force roughness, Ra=6.5mN, Rq=8.25mN；And relative to biomethanics roughness, Ra=0.0274kN/m, Rq=0.0395kN/m.As a result indicate for the in vivo FNE biopsies based on power inhomogeneities with good in Diagnosis of Thyroid Carcinoma Property and the FNE devices of Malignant Nodules, system and technology following application.Therefore, it can be pipe that FNE devices, system and technology, which ensure, The important diagnostic tool of thyroid cancer is managed, without ultrasonic instrument instrument or the qualified FNAC virologist of acquisition.Alternatively, FNE devices, system and technology can be used in auxiliary diagnosis.

Palpation is the initial examination of thyroid cancer.After solid nodules are found by palpation, clinician usually requires that Patient carries out Secondary Screening, and the Secondary Screening is typically thyroid ultrasonic examination.Ultrasonic examination can be used in determining first shape In glandular tissue tubercle is not can touch with the presence or absence of as low as 1mm.Ultrasonic wave is a kind of mechanical imaging pattern, because there is density Or the reflection from tissue occurs for the place of the significant changes of modulus of elasticity.Sonographer can be with document thyroid gland It whether there is calcification in tubercle, because these hard dense parts in solid nodules are related to thyroid various cancers.If Tubercle (such as being understood by sonographer) is shown by ultrasonic examination, then requires that patient carries out three-level examination, i.e. pass through The biopsy of FNAC ultrasonic wave added.In the process, the hollow needle with concentric stylet is inserted in tubercle several times, simultaneously Withdraw stylet so that the cell of small sample is introduced into pin by the suction as caused by stylet.Cell will be generally extracted out to be applied to On slide, assess and diagnose to prepare to be used for the subsequent cell based on cytomorphology.

The concept of example 1 allows thin to extracting out without ultrasonic device, the subjective evaluation of ultrasonoscopy or virologist In the case of the analysis of born of the same parents diagnosis is proceeded to from initial examination.In addition, the resolution ratio of FNE devices, system and technology is better than ultrasound The accessible resolution ratio of ripple.When the pin of FNE devices in example 1 passes through material, to quantifying for the power that is applied on the pin Analysis can distinguish health tissues and malignant tissue.Therefore, the concept of example 1 can be used alone, or for strengthening existing skill The Sensitivity and Specificity of art.

When pin enters tissue, process follows distinctive pattern.First, pin promotes tissue, so as to steadily increase insertion Power.During this stage, before the limiting range of stress is reached, metaplasia.Then, needle-penetration tissue, then organizational slack, now Pin is advanced into tissue.Pierce through the drastically decline for being considered as insertion force.In the presence of three on the pin acted in insertion soft tissue Plant main power, i.e. rigidity power, frictional force and cutting force (at needle point).The total power inserted for pin depends primarily on tissue Local biologic mechanical characteristic.Therefore, because tactile caused by this total power is related to the local biologic mechanical characteristic organized.Pin There is marked difference between the tactile in tactile and insertion malignant goiter knurl in insertion health tissues.For example, FNA pins are inserted Enter tactile in health tissues and be similar to insert a needle into gelatin, and the tactile in FNA pins insertion malignant tumour is similar to pin Insert in raw pears.

Under the tens of μm of levels below with ultrasonic wave resolution ratio, there are significant changes in the mechanical characteristic of material.In cellular water Under flat, cancer cell is more obedient to (compliant) than health tissues；However, tumour generally difference submissiveer than health tissues.This with cancer The apposition that disease is observed during developing is consistent with the increase for intersecting combination.The mechanical response of tissue is by surrounding matrix Rigid structure element (for example, collagen) in (peripheral stroma) is occupied an leading position.In concept, in pin When point passes through the region of healthy cell, the elastic force measured is by less than through elastic force during health tissues, but through periphery During matrix, pin measures the power being significantly higher than through during health tissues.Show in addition, normal galandular epithelium and benign real venereal disease become Unimodal but different Stiffness Distribution.On the other hand, malignant tumour can show the mechanical heterogeneity for meeting histological appearance, with And the characteristic relatively low stiffness peak value in the region of the tumour cell with tight clusters and less intermediary's matrix.Final result is When pin passes through Malignant Nodules, the inhomogeneities of local force is dramatically increased with tens of μ m in size level.

In the method (in this this case, referred to as ultrasonic elastograph imaging or UE) of referred to as elastogram, it has thus been sought to which extension is super Sound wave is used for the ability for measuring quantitative elastic characteristic in vivo.In UE, via ultrasonic measurement elastic deformation, and produce Deform the local stiffness for resolution ratio (under 5-12MHz 0.2 to 0.3mm) computation organization with medical ultrasonic.In this chi Under very little level, health tissues show the rigidity lower than tumour.However, becoming because UE is measured via ultrasonic examination (mm size levels) Shape, therefore it is unable to detect that the inhomogeneities presented with tens of μ m in size level.

In other direction, AFM has shown that the viscoelastic property of detection cell and the ability of space reflection cyto-mechanics characteristic, And explore for diagnostic application.However, AFM is can not to detect hypodermis in vivo (for example, the thyroid gland knot of patient Section) sufacing.

Example 1 is illustrated detects inequality with tens of μ m in size level ability helping to detect the depth of material property in vivo The investigation of even property.Generally, for one or more embodiments, for example, it is inserted into life with pin (or other detecting elements) The depth bounds that distance in thing tissue is associated can correspond to the length of pin, and can be greater than about 600 μm, for example, about 1mm or bigger, about 5mm or bigger, about 1cm or bigger, or about 2cm or bigger, and it is up to about 5cm or bigger, and space Resolution ratio can be less than about 1mm, for example, about 0.5mm or smaller, about 0.3mm or smaller, about 0.2mm or smaller, about 100 μm or It is smaller, about 80 μm or smaller, or about 40 μm or smaller, and as little as about 10 μm or smaller.Investigation is related to mapping insertion force, is used for Qualitative assessment insertion force and structural heterogenity.Therefore, diagnostic techniques is introduced, the internal cancer diagnosis for solid tumour is included The diagnostic techniques of (for example, thyroid gland, breast and liver).

A kind of base position in FNA pins is developed in investigation has the FNE devices of calibration force snesor.

Methods described uses two kinds of technical identifications.In the first technology, the measurement accuracy and resolution ratio of device utilize mm grades The similar sample of gelatin substrate represents that the raw pears in health tissues and embedded gelatin represent that the tumour in original health tissues is come Initially determine that.

In the second technology, ultrasonic neck phantom is used to test poor for the biomethanics of different types of thyroid nodule Different FNE devices.Portable ultrasonic device is used to guide FNE devices.With the simulation fluidity knot in FNE device detecting ultrasonic models Section and solid nodules.Compared with the region in fluidity tubercle or model corresponding to healthy parathyroid tissue, as a result show with Distance (one dimension force roughness in solid nodules：Ra=6.5mN, Rq=8.25mN) and biomethanics roughness (Ra= 0.0274kN/m, Rq=0.0395kN/m) parameter significantly higher power change.The result is realized with micrometer level.

FNE devices

Fig. 3 A to Fig. 3 C illustrate the FNE devices of example 1, and wherein Fig. 3 B are the expander graphs of some components of Fig. 3 A device, And Fig. 3 C are the descriptions for the device that how can hold Fig. 3 A.

Illustrate to connect the typical case No. 25 that can be interchangeably mounted on the head of FNE devices using standard Luer in Fig. 3 A Gauge FNA pins (U.S. Becton, Dickinson and Company).Pin narrower (for example, about 500 μm of external diameters) is with reduction Bleeding, and length is enough to puncture thyroid full depth (for example, about 51mm).In this example, the selection profit of standard pin The low cost and interchangeability provided with the pin industry being confirmed.In addition, the high homogeneity of manufacture pin is operated herein Cause repeatable power in pattern.

As illustrated in fig. 3b, cylindrical piezoelectric transducer (PZT-5A, Boston Piezo-Optics Inc., USA (boston, U.S.A piezoelectricity Optical Co., Ltd)) it is arranged in the head of Fig. 3 A FNE devices.Piezo tube has electroless nickel electrode (pipe Inner and outer wall be used as output electrode), the nickel electrode has 3117pF (± 20%) electric capacity calculated in theory.By In the high rigidity, simplicity and low cost of piezo-electric crystal, piezo-electric crystal is selected as force snesor.Crossed in usual measurement (across) during the voltage of piezo-electric crystal, the electric capacity of sensor can highly influence such signal, and this can result in delayed (hysteresis) and both drift.Therefore, selection is operated by measuring electric charge q, and the electric charge is past in theory and practice Toward all with stress linear correlation.According to equation (1), the electric charge produced at piezo-electric crystal and the power (F) that acts on device into Ratio, wherein for PZT-5A, d₃₁It is piezoelectric constant (d₃₁=-171x10^-12C/N), r_oIt is the outer radius (r of cylinder_o= 0.0625 "), r_iIt is the inside radius (r of cylinder_i, and h is the axial height (h=0.500 ") of cylinder=0.0425 ").

Calculate preferable conversion factor -5.1x10^-9C/N.In the FNE devices of example 1, electrode size is decreased to be adapted to FNE Device, and epoxy resin is for installing electrode, so that actual converted factor is decreased into -4.3x10^-9C/N。

The end of transducer is fixed to head, and the head is fixed to 3D and prints holder again, as shown in Figure 3 B.Fixing Device using SolidWorks 2013 (France, Dassault Systemes SolidWorks Corp) designs and by Makerbot Replicator2^TMDesktop 3D printer (U.S., MakerBot Industries) 3D printing.Transducer it is defeated Go out end using and the insulated copper wire that is attached of a small amount of silver-colored conductive epoxy resin (U.S., ChemtronicsInc.) to be connected to standard same Shaft cable plug (Bayonet Neill-Concelman) (BNC) cable.5M Ω resistors are electrically connected across transducer parallel connection, For high output impedance.

The advantage of fixed position of the transducer accommodation in shell is, signal of the processing from transducer is less multiple It is miscellaneous and more accurate, without adjusting measurement based on the distance away from pin, it will be needed if transducer is not fixed in shell Measurement is adjusted based on the distance away from pin.

Transducer accommodation is in another advantage in shell, compared with the situation that sensing element is located at needle point, pin Diameter can be smaller.

Transducer accommodation is in the another advantage in shell, pin can be professional standard pin (for example, producing in enormous quantities ), thus reduce cost and increase availability and uniformity.

Another advantage of the transducer accommodation in shell is that pin can extend to material substantially along its length In, rather than be prevented from extending in material, it will be prevented from extending in material if sensor is installed along pin.

Experimental provision

Fig. 4 illustrates the experimental provision measured for the FNE using FNE devices 410.When needing direct measurement electric charge, electricity Lotus amplifier is intended at low frequency turn drop.Therefore, instead of example 1, selection is with time measurement electric current and to electric current in number Quadratured in value to determine electric charge, and thus improve system in low-frequency performance.

The output end of FNE devices 410 is connected to low-noise current preamplifier 415 (SR570, U.S. Stanford Research Systems).Output current signal is amplified with 10nV/A gains in the case of bandwidth 0.03Hz to 300Khz.Make Digitized with data collecting card 420 (NI USB 6259, National Instruments (National Instruments, USA)) The current signal of amplification.Digitize current signal and in dedicated computing device 425 (Intel's Duo 2,6400@2.13GHz, 2GB RAM, 32 MS Windows Vista Home Premium SP2) on (states of the U.S. of LabView 2013 of self-defined driver write that run Instrument company of family) it is integrated, the dedicated computing device is used for the data acquisition and position control of single shaft linear movement level.

The linear movement of FNE devices 410 is by single axis actuator level (stage) 430 (LX26, Sanjiao Group Co., Ltd, day This Suruga Seiki (Misumi Groups Inc., Suruga Seiki Co., Japan)) control, the single shaft cause Dynamic maximum length of travel of the device level with positioning repeatability and 200nm as defined in ± 5 μm of manufacturer.The level is mixed by two-phase Box-like stepper motor (applying Decathlon Production (Applied Motion Products Inc., USA) in HT17-068, the U.S.) Driving, the two-phase hybrid stepping motor is controlled by servomotor controller (applying Decathlon Production in AM3540i, the U.S.) System.It is at least 10 μm -12 μm with the positional accuracy of the linear grade of encoder assembles.

Power is calibrated：Due to the succinct simplicity of method, gravity load is selected.Using between electronic scale weighing 0.5g and 15g Quality (m), and use F_g=m g calculate gained gravity F_g, wherein g=9.81m/s²It is gravitational constant.The quilt of FNE devices 410 Quality that is vertically-mounted and then glossily loading and unload calibration.For each in the quality of calibration, measure to conduct oneself with dignity The piezoelectric charge change of power loading.Fig. 5 draws the power and piezoelectric charge measured, wherein also illustrating the one of calibration constants (N/C) Order polynomial (linear) fit slope.Table 2 shows the value drawn in Figure 5.

Table 2

Power calibration measurement is completed with 2nA/V pregain using 0.03Hz to 100kHz bandpass filter. After calibration procedure, load the quality of calibration again, and the power measured by FNE devices 410 be verified as with via F_gThe power that=m g are calculated is consistent.

Power is measured：Power measured value is recorded with 1,000 sample (kS) per second, while with 12mm/s translation FNE devices 410, so that There is provided per 12 μm of sample resolution.Following variable storage is on computer：Timestamp (s), level position (mm), integrated current (A) With power (N).Typical time of measuring is maintained at 8s/ and moves mark (per trail) below.

The feature for the power inserted for pin：The feature of power (is included to many percutaneous therapies during pin inserts soft tissue FNAC preoperative plan and actual surgery simulation) is extremely important.It is in the presence of description description pin-tissue interaction mechanism With the theoretical model of several exploitations of power and shifted version.

Conceptually, the pin in insertion vacuum will be subjected to inertia force F_inertial(t).After in insertion material, material will Resistance is punctured so that pin is subjected to puncturing power in opposite direction.It is by its these insertion force for being subjected to order：Description is by organizing The F of power caused by deformation_stiffness(t), it is subjected to the elastic restoring force at for needle point；Due to cutting when pin separates tissue Cut caused F_cutting(t), it is subjected at needle point and near needle point；And description slips over the tissue that pin has been penetrated in pin wall When friction F_friction(t), it is acted on due to the relative motion between pin and tissue on pin wall.Cutting force is included by cutting The power cut the plastic deformation of behavior generation and produced by the tissue rigidity of needle point.Frictional force is the Internal biological mechanics of tissue The function of characteristic (for example, rigidity) and the characteristic of pin wall surface.Each in these power, which can be expanded to, also describes higher Level behavior.For example, F_stiffness(t) non-linear rigidity or plastic deformation of tissue can also be described.

The combination pin insertion force relative to given material is presented in equation (1 ').

F_needle(t)=F_stiffness(t)+F_cutting(t)+F_friction(t)+F_inertial(t) (1’)

The total power measured is the function of the biomechanics characteristic of respective organization.

As a result with data analysis-similar sample

Preliminary FNE power is carried out using the special sample of the raw pears pieces of the 10mm cleaned in embedded 6% gelatin (gel) to survey Amount.This sample is similar to the thyroid tumors surrounded by health tissues.Commercial tasteless jelly powder (Kellogg Company of the U.S. (The Kroger Co., USA)) it is used to make gelatin, wherein 1.2g dry gelatin powder is dissolved in about 20mL boiling water.The red food of addition With pigment with clear differentiation pears layer.Gelatin and pears are positioned over index type 1 vial (15x45mm, Fisher Scientific International, Inc., USA) in and allow solidification 2 hours.After gelatin solidification, sample is immediately For the FNE measurements under atmospheric environment (at room temperature and atmospheric pressure).Additional samples omit pears.

Fig. 6 is towards the inclusion of vial, through gelatin and through above-mentioned system in the pin of FNE devices 410 through air The curve map for the exemplary force distribution that pears in standby sample are obtained when advancing.Initially, when pin is advanced through air, indicate substantially Zero power.At the point 610 labeled as " contact point ", pin enters gelatin.Power distribution is illustrated in slightly inclining when pin passes through gelatin Tiltedly, the resistance acted on by gelatin on pin is represented.The smooth power distribution means of gelatin the small change (example due to mechanical property Such as, mechanical property is uniform), therefore there is minimum force change.When next pin is being selected at 615 into pears, such as pass through point Indicated by the small arrow in power distribution between 615 and point 625, compared with the power distribution in air and gelatin, the power distribution Show significant inhomogeneities.Show to be in the amplifier section that pears layer Nei Shili is distributed in pin in Fig. 6 illustration, wherein can See, feature of the resolution ratio identification with different mechanical properties less than 20 μm can be used.

In practice, due to the metaplasia occurred during pin is inserted, therefore the original absolute position of tissue may be omited Micromodification becomes.It is smaller in view of the deformation in tissue, it can use path x (t) that F (t) is converted into F (x), this allows to draw power F (x) and apart from d (x) distribution maps.

The electric charge that the current signal representation measured is produced according to i=dq/dt at device, wherein i are electric current and dq/ Dt is the charge variation relative to the time.According to dq/dt ∝ d₃₁(dF/dt), charge variation is proportional to power change.And dF/ Dx=dF/dt*dt/dx produces i ∝ d₃₁V dF/dx, wherein dF/dx have specific stiffness (N/m), d₃₁It is piezoelectric constant, v= Dx/dt is speed, and i is the electric current measured.Because piezoelectric constant and speed can be considered as keeping in whole measurement It is constant, so current signal is proportional to rigidity (dF/dx), power change (dF/dt) of some of them contribution from time correlation.

When attempting the inhomogeneities of quantification area portion of branch office biomechanics characteristic, the power mould of one-dimensional roughness parameter is used Intend, referred to as power inhomogeneities (H_F) and rigidity inhomogeneities (H_S).For the power (F (x)) according to equation (2) and (3) and for According to equation, (first derivative (dF/dx) of the power of 2 ') and (3 ') calculates H using Matlab_FAnd H_SOne-dimensional parameter.

Mean force inhomogeneities；

Mean rigidity inhomogeneities；

The average value of-power

The average value of the first derivative of-power

The number of N- data points

Root mean square power inhomogeneities；

Root mean square rigidity inhomogeneities；

Mean force inhomogeneities (the H calculated_F,a) and root mean square power inhomogeneities (H_F,q) parameter is in units of mN.Rigidity Inhomogeneities (H_S,a) and root mean square rigidity inhomogeneities (H_S,q) in units of kN/m.As shown in equation (2), one-dimensional mean force Inhomogeneities H_F,aBe according to evaluation length above average line power distribution in mean derivative a little (according to standard： ASME B46.1-1995、ASME B46.1-1985、ISO 4287-1997、ISO 4287/1-1997).Such as institute in equation (3) Show, root mean square power inhomogeneities H_F,qIt is being averaged for measured derivative that is being obtained in evaluation length and being measured from average line The root-mean-square value of value.

Using 5 moving average filters, come from using the smooth function processing in Matlab in Fig. 6 and draw experiment As a result initial data.Fig. 7 A draw smoothed data as air (curve 705), gelatin (curve 710) and pears (curve 715) power of data and range distribution (carrying out baseline adjustment using single order fitting of a polynomial).In addition, using in Matlab from First derivative of the code computing power relative to distance write is defined, wherein code calculates the derivative between 3 data points.In figure In 7A, compared with air section and gelatin layer, the significantly higher change of the mechanical characteristic in pears layer region is apparent.Fig. 7 B are shown Power inhomogeneities (the H calculated for the power distribution shown in Fig. 7 A_F,a、H_F,q) parameter.Bar 720,735 represents air, bar 725th, 740 gelatin and the expression pears of bar 730,745 are represented.Fig. 7 B quantitative descriptions are compared with air and gelatin region, in pears layer The higher variation of mechanical characteristic.Fig. 7 C show the first derivative curve map of a part for Fig. 7 A power distribution.Power is relative to distance First derivative have and rigidity (N/m) identical unit.Such as it is clear that in air from Fig. 7 A (curve map 705 and 710) Change minimum with the power in gelatin layer.Therefore, Fig. 7 C first derivative curve, which illustrates air and the derivative line of gelatin, (is respectively Curve 750 and 755) overlap each other, but pears region shows the significantly higher change (curve 760) of first derivative.Pass through Fig. 7 D In rigidity inhomogeneities parameter show these change quantization.With other regions (air, bar 765,780 and gelatin, bar 770th, 785) compare, the high rigidity inhomogeneities value (H of pears layer (bar 775,790)_S,a、H_S,q) represent mechanical characteristic in pears layer High localized variation.

By for similar gelatin and pears sample FNE devices 410 realize preliminary power measurement contemplate FNE 410 (with And the other embodiments of FNE devices 110) in the inhomogeneities of dividing tissue biomechanics characteristic to detect tumour and other not advise The promising result of ability in terms of then.

As a result with data analysis-model

Fig. 8 is provided for further assessing the anthropomorphic neck phantom that FNE devices 410 are characterized and diagnosed in thyroid tumors (CIRS-074 Thyroid ultrasound training patterns, american computer is melted into as frame of reference Co., Ltd (Computerized Imaging Reference Systems, Inc., USA)) diagram.The diagram and Fig. 8 B that Fig. 8 A provide model provide model Ultrasonoscopy.Anthropomorphic neck (model) is the thyroid gland biopsy procedure of the progress ultrasonic guidance specially designed for resident doctor Training tool and put into practice medium.Model contains the thyroid gland in anthropomorphic neck.Lobus glandulae thyroideae contains diameter about 10mm extremely 12mm two solid nodules (waiting the hard lesion of echo) and diameter about 8mm four fluidity tubercles (tumour).Model is by wrapping In proprietary elastomerIt is made.Elastomeric material by the acrylamide and N in vacuum degassed liquid solution, The polymerization of N'- methylene-bisacrylamides is produced.By the glass microsphere particle comprising aluminum oxide, boron nitride and various concentrations with Make solid and liquid particles permanent suspension to realize the local ultrasound change of reflection in material.Although the material under tens micron orders Look not exclusively as parathyroid tissue, but model closely and provides local mechanical characteristic with thyroid gland size level The cast material of (centimetre) change.

(the plus ultrasonic systems of SonoSite 180, U.S. SonoSiteInc. are used under real-time ultrasound guiding) to complete FNE devices 410 are inserted in model neck.The localized variation of the acoustic impedance (Z) of the reflective representation material of ultrasonoscopy.Acoustic impedance (Z) be material density and Young's modulus function.Because Young's modulus is the measurement of material stiffness, therefore in audiograph The contrast of the inhomogeneities arrived represents the localized variation of the biomechanics characteristic in material.Therefore, this Ultrasound Model is served as and is used for The localized variation of mechanical characteristic inhomogeneities is tested to assess the good sample of FNE devices 410.

For being measured using the exemplary force of FNE devices 410, by being individually manually inserted into pin, while observing on ultrasonic screen Corresponding tubercle and determine insertion angle (usual 90 ° ± 10 °).Then, FNE devices 410 are according to predetermined insertion angle-determining Insertion path (as shown in Figure 8 A) on align.Using holder by ultrasonic probe (C11/7-4 curve pattern ultrasonic transductions Device, U.S. SonoSite Inc. (C11/7-4Curved-Array Ultrasound Transducer, SonoSite Inc., USA), in fig. 8 a labeled as " US probes ") it is fixed on the clear visual field that required orientation sentences maintenance insertion path.For each Power is measured, and uses HD video cameras (pixel of Canon T3i, 18MP, 1920 × 1080,30 frame (fps) per second) record audiograph screen. Fig. 8 B show the example of the ultrasonoscopy recorded during measuring.As a result show, model cervical specimens are applied to from ultrasonic probe On pressure it is minimum so that be not significantly affected by power measurement.12mm/s constant insertion speed is used in the measurements.This value is main Based on the typical insertion speed observed during FNAC biopsies.

Fig. 9 A show to compare with reference standard (the healthy parathyroid tissue of simulation, curve 915), through in model neck The representative power distribution (curve 910) of the pin of FNE devices 410 of fluidity tubercle.Illustration shows the extended edition of a part for power distribution This.Fig. 9 B show the ultrasonoscopy of the fluidity tubercle in model neck, wherein indicating insertion path (" needle path footpath ").Fluidity tubercle (tumour) has about 8mm diameter.Force curve (Fig. 9 A) is made up of three main regions in needle path footpath.When pin passes through air, Region (a) (beginning in insertion path) shows essentially a zero power.Needle-penetration model, and (start in region (b) along slotting Enter path and slightly pass through 5mm) in, exist with pin through artificial skin and then across corresponding constant-slope area of soft-tissue material Domain.Pin then enters fluidity tubercle at Fig. 9 A Far Left black arrow 920 (and Fig. 9 B Far Left black arrow) place, and And before fluidity tubercle (Fig. 9 A rightmost black arrow 925 and Fig. 9 B rightmost black arrow) is left, through Fig. 9 A Region (c) in fluidity tubercle.Smaller slope variation compared with region (b) in region (c) is due to and artificial soft tissue The relatively low resistance that the resistance of material compares the fluid in fluidity tubercle causes.The smoothness of curve in region (c) confirms The low heterogeneity (high uniformity) of fluid, and in the tubercle through fluid filling the pin of FNE devices 410 undergone it is easy Puncture.

The power distribution that the pin of FNE devices 410 is inserted through " the non-nodules region " of model is used as reference standard, and shows big Inhomogeneities is measured, as illustrated in figure 9 a.This is probably because the uneven essence of model elastomeric material in this region (this is also apparent from unshowned other ultrasonoscopys).

Figure 10 A show the representative power distribution through the pin of FNE devices 410 of the solid nodules in model neck.Figure 10 B show The ultrasonoscopy of the solid nodules gone out in model neck, wherein indicating insertion path (" needle path footpath ").Solid nodules in model It is designed to the characteristic of the true thyroid cancer of ultrasonic simulation.Solid nodules have about 15mm diameter.Shown in Fig. 9 A The distribution of fluidity tubercle power, essentially a zero power is used in (region (a)) in atmosphere, and exist and be used for through soft tissue The constant-slope in (region (b)).Pin subsequently enters the region with more inhomogeneities (at about 22mm, with white on Figure 10 A White arrow mark on color arrow 1010 and Figure 10 B), and cross solid nodules.FNE needle-penetration solid nodules are (about At 34mm, marked at the black arrow 1020 in Figure 10 A and with " * " at black arrow in fig. 1 ob), and pass through Solid nodules (region (c)).Compared with the knuckle areas (Fig. 9) of reference standard and fluid filling, the power through region (c) is distributed Show the much bigger power change in solid nodules region.Illustration in Figure 10 A shows the enlarging section in the region (c) in illustration Point.

Figure 11 shows the difference of the power distribution in two kinds of knuckle areas (fluidity, reality) and reference standard region.Figure 11 tables Show that common zoom is used for the different piece from Fig. 9 A and Figure 10 A the power distributions extracted compared side by side.Right side shows correspondence ultrasound Image, represents the pin conduct of FNE devices 410 for response curve.It was observed that solid nodules and the significant difference of fluidity tubercle：It is real Property the distribution of tubercle power (b) displaying be distributed (a) with fluidity tubercle power compared with significantly higher power change.The power distribution of reference standard region (c) also indicate due to power change caused by the uneven essence of artificial soft tissue area.

Figure 12 A are shown for solid nodules (curve 1205), fluidity tubercle (curve 1210) and reference standard (curve 1215) comparison of baseline adjustment power distribution (Δ F/dx).Solid nodules force curve 1205 shows that most high-tensile strength changes.As also in figure See in the audiograph of model solid nodules in 10B, power change is due to the non-of the mechanical characteristic in the solid nodules of model Uniformity causes.

Figure 12 B provide the quantization of the power change for Figure 12 A reality, fluidity and reference standard curve.In Figure 12 B simultaneously Parallelism is compared with the power inhomogeneities parameter H that the baseline adjustment power distribution for Figure 12 A is calculated_F,a、H_F,q.Such as can in Figure 12 B See, the mean force inhomogeneities H of solid nodules (bar 1230,1245)_F,aWith root mean square power inhomogeneities H_F,qBoth ratio streams of value Property tubercle (bar 1225,1240) and reference standard (bar 1220,1235) the high several values of value.

Figure 12 C are shown for solid nodules (curve 1260), fluidity tubercle (curve 1250) and reference standard (curve 1255) comparison of the first derivative of baseline adjustment power distribution (dF/dx).Power relative to translation distance first derivative with it is one-dimensional Organize rigidity (N/m) share same units, and dF/dx change and material biomechanics characteristic localized variation into than Example.Due to the highly non-uniform property of the mechanical characteristic in solid nodules, compared with fluidity tubercle and reference standard, solid nodules First derivative curve 1260 shows significantly higher change.If the instruction of " 36 μm " between two arrows in Figure 12 C Find out, the micrometer-class that analysis changes with biomechanics characteristic can be illustrated from the first derivative curve.

Figure 12 D provide the quantization of the power change for Figure 12 C reality, fluidity and reference standard curve.In fig. 12d simultaneously The power inhomogeneities parameter H that first derivative power distribution of the parallelism compared with the baseline adjustment for Figure 12 C is calculated_S,a、H_S,q(reality knot Save bar 1275,1290, fluidity tubercle bar 1270,1285 and reference standard bar 1265,1280).Due to the mechanics in solid nodules The significantly high localized variation of characteristic, compared with fluidity tubercle and reference standard, it is apparent that the rigidity in solid nodules Inhomogeneities is significantly higher.

Therefore, rigidity inhomogeneities parameter value can be used in quantifying for reality or fluidity tubercle (tumor nodule in occlusion body) Distinguish.

Discuss

Tumor development in health tissues is main along with extracellular matrix (ECM) and eucaryotic cell structure (about 1 μm to 10 μm) In complicated small structure change, this (up to hundreds of microns) can develop into differentiable mechanics under macrostructure's level Response.Some biomechanical characterizations of reality thyroid nodule are associated compared with high likelihood with malignant tumour.Most common type Thyroid cancer, i.e., it is hundreds of microns of complex branches mastoid process that papillary carcinoma, which contains size, the mastoid process tool There is the fibrovascular core covered by individual layer tumour cell.Compared with normal thyroid gland parenchymal tissue, such as mamillary first shape The Malignant Nodules of gland cancer have shown vascular distribution in increased tubercle, irregular permeability cancer beside organism (margin), many The presence of individual microcalcifications and the high shape of width than being measured in transverse dimensions.Because FNE devices 410 can be with than it The achievable resolution ratio of its mechanics method higher resolution ratio explores the biology of the tumour in mastoid process and calcified regions Mechanical heterogeneity, helps to combine other omen tumour markers to predict thyroid tumors so quantitative FNE measurements are expected Behavior.

Table 3 provides the comparison of the technology (including FNE) of measurement Mechanical Properties of Soft Tissues.With other mechanical imaging mode phases Together, FNE methods can be applied to other palpable cancerous lesions independent of ultrasonic wave, for example, breast and hepatic disease.

Table 3

Example 1 is illustrated in the reality distinguished between gelatin substrate (uniform) and raw pears (uneven) and in neck phantom Property (uneven) and fluidity tubercle (uniform) between biomechanics characteristic and FNE devices 410 during inhomogeneities distribution Resolution ratio and measurement accuracy.Examining for biomechanics characteristic inhomogeneities is measured under cell and organisational level in order to further assess Disconnected meaning, can in vitro be tested for the parathyroid tissue patient's sample of excision.What can be removed according to operation is fresh Benign and malignant Patients with Thyroid Tumor sample produces the database of rigidity and inhomogeneities distribution so that tumour FNE data are with swelling Knurl is associated with classification cell pathology by stages.Follow-up internal test to mankind's thyroid nodule can be used in research in FNAC Operating parameter under the actual state of process, and further improve and develop FNE devices 410.It should be noted that solid tumour can It is benign (for example, adenoma sample tubercle or filter blocking adenoma) or pernicious (papillary thyroid carcinoma, follicular carcinoma etc.), and contains The lesion of fluid may not be benign (for example, capsule papillary thyroid carcinoma).Therefore, other researchs are comprising in vivo and body The tumour of tumorectomy or tumor resection, lesion, other scramblings, cancer beside organism and health tissues are commented outside Estimate, to characterize power expected from FNE devices 410 in actual sufferer.It should be noted that assuming that metaplasia makes comparatively small to total power Contribution and therefore in example 1 in detail consider；Become however, different amounts of tissue may be present in further improved method Shape, these metaplasias can be comprised in resultant force model.

The FNAC and FNE of combination handheld portable devices are envisaged in the disclosure, described device can modify For other percutaneous methods for diagnosis and treatment in vivo.

Example 2

Another FNE devices

Figure 13 A illustrate another prototype of FNE devices 1310 and how can hold the diagram of described device.Figure 13 B are Represent the block diagram of FNE devices 1310.As shown in Figure 13 B, FNE devices 1310 include piezoelectric force transducer in the form of cylinders 1320 and No. 25 gauge FNA pins 1325 of hand-held tool are installed to by the cylinder of force snesor 1320.Use FNE Device 1310 is based primarily upon structural homogenity quantitative measurment pin insertion force, to detect benign thyroid nodules and pernicious thyroid gland Tubercle.Component 1330 is also illustrated in Figure 13 B, the component can be incorporated in the shell of FNE devices 1310, or is for example connected by line It is connected to FNE devices 1310.Component 1330 includes charge amplifier 1335, (one or more) position sensor 1340, microprocessor Device 1345 and USB (USB) interface 1350.Usb 1 350 is connected to computing device 1355 and (is shown as flat board calculating Machine).Usb 1 350 can be wired or wireless.In other embodiments, usb 1 350 with substitute it is parallel or Serial wired or wireless interface is replaced.

Charge amplifier 1335 produces the voltage proportional to insertion force.This voltage and from (one or more) position The data of sensor 1340 are collected by microprocessor 1345 (computing device) and are sent to safe computing device 1355, described The computing device 1355 of safety provides data processing, data display, data storage, battery supply and cellular communication.

Figure 14 A are the schematic diagrames for representing the charge amplifier 1335 for FNE devices 1310.Piezoelectric ceramics and crystal show In response to the charge displacement of pressure applied.Received at charge amplifier 1335 at input 1410 and be applied to piezoelectric forces biography The instruction of the pressure of sensor 1320.The output voltage at output end 1420 of charge amplifier 1335, the voltage with input The instruction of what is received at 1410 the be applied to pressure of piezoelectric force transducer 1320 is proportional.On the voltage and FNA pins 1325 Insertion force it is directly related.Figure 14 B are the images of the prototype of charge amplifier 1335.

The cylinder or pipe of piezoelectric force transducer 1320 are divided into permission device and not only measure axial insertion force, but also measure The quadrant (quadrant) of laterally inserted power, so as to provide substantially instant to operator in the case where not being inserted directly into pin Feedback.It can also allow for due to angled insertion that software correction pin position and compensation pin are scratched on being later inserted into the information of power It is bent.

Compared with FNAC, FNE can provide the elastograph imaging method of real-time quantitative with 40 μm or bigger of positioning precision.Institute State technology has cost benefit (substantially cheap 100 times) compared with ultrasonic wave, MRI or computed tomography (CT), but divides Resolution is ten times of ultrasonic wave, MRI or CT.In addition, FNE devices 1310 are more much smaller than ultrasonic wave, MRI or CT equipment.Proposed Insertion force elastograph imaging method size level is transitioned into tissue, organ level from individual cell level.The combination of this size level makes FNE, which turns into, is applied not only to inexpensive diagnosis, but also for the interesting methods of the elastogram research in terms of intermediate sizes level, Wherein in intermediate sizes level, material property greatly changes.The technology can be applied to various applications, for example, to disobey Ultrasonic method is relied to detect palpable cancerous lesion (breast, liver).Furthermore it is possible to recognize tumour using FNE devices 1310 Or Treatment decsion is made during other scramblings, and can be by adding features to FNE devices 1310 in FNE devices 1310 are during use treated.

Due to the collagen in matrix and frequent doped calcium, tumour shows uneven elastic behavior.Such region Elastic behavior changes the order of magnitude from healthy cell, and therefore, it is possible to for example be detected by diagnostic ultrasound imaging, and even It can be arrived during FNA pins are inserted by the hand qualitative detection of clinician.Because the elastic inhomogeneities of tissue can cause not Uniform pin insertion force, therefore the method proposed seeks spatially to map quantitative insertion force and is used as inexpensive cancer and examines It is disconnected.

The power inserted in pin in biological tissue on hour hands can be described as inertia force, elastic force, frictional force and cutting force Summation.Usual inertia force is smaller, because substantially inserted with constant speed, and therefore, it is possible to ignore in most of analyses The inertia force.Elastic force describes the restoring force that tissue response is applied in elastic deformation on pin.Frictional force description is inserted in pin For the resistance of speed when entering tissue, and it is with speed and proportional with both surface areas of pin for organizing to contact.Cutting force Describe pin under the surface side driven deeper into when separated action will be organized at needle point.Description is needled into uniform formation Typical cutting Model the characteristics of be single Hookean region, subsequent puncture event and pin pass through tissue when friction and cut Cut region.However, this model does not consider that material is probably uneven, and may occur when destroying skin or another material Multiple puncture events.For example, Figure 15 shows the measurement response for the pin being pierced into the heterogeneous material of ox muscle, wherein initial structure Puncture is followed of some less puncture events, as the power after by initially piercing through fluctuate it is indicated.When When inserting a needle into homogeneous material, in the absence of this series of features.Therefore, FNE devices 1310 provide determining for structural heterogenity Metric.

Resistor coding device (potentiometer) can be used to map the position of pin, wherein measuring resistance and in the adc by the electricity Resistance is converted into digital value.(for example, many microcontrollers have integrated ADC).Linear potentiometer with 4cm strokes being capable of numeral Change to 10 (bit) precision to realize such as 40 μm of positioning precision.Ultrasound is provided using this positioning precision of inexpensive component About ten times of fine resolution ratio of the diffraction limit of ripple, MRI or CT.Therefore, FNE devices 1310 are the desired sides of elastogram Method.Size level is transitioned into tissue, organ level by the insertion force elastograph imaging method proposed from individual cell level, and ultrasonic Ripple, MRI or CT do not have this ability.

If producing the interference with optional ultrasonic guidance for the magnetic sensing that pin is positioned, the sense of replacement can be used Survey mechanism, the sense for the pin insertion depth that such as 6 axle gyroscopes with 3 axle accelerometers and the secondary harmonics by pin change Survey, this depends on the depth that pin extends in the tissue.

Example 3

The establishment of database

Organize rigidity significant changes between the various pieces of human body.For example, soft tissue elastic force is less than for marrow 0.1kPa, for brain tissue between 0.1kPa and 1kPa, for fat between 1kPa and 10kPa, be about for muscle 10kPa, and it is more than 20kPa for bone.In addition, as described above, scrambling shows different tissues rigidity, and can be with Time change.For example, in tumour growth, tumour changes material property.

At present the most reliable prognosis tumour marker that clinically uses be neoplasm staging and classification (for example, referring to for The benign table 4 to pernicious thyroid cancer tubercle, wherein benign be designated as " 1 "；Rigidity is compared with normal structure).

Table 4

Such classification and follow-up diagnosis are carried out by the FNA of core biopsy or tumor mass, but in these types It is classified on sample and by stages possible inaccurate.The Cytoskeleton of cell rigidity and cell is closely related.Cell rigidity is swollen Play an important roll in tumor activity, invasion and transfer；However, tissue biological's mechanics and inhomogeneities can be used to predict tumour The more quantitative marker of behavior.

Next discuss for making neoplasm staging and the classification technology related to tumour FNE measurements.

(AFM can be used by the thyroid nodule that is cut off from 50 corrective surgeries and with Young's modulus using FNE analysis It is determined that) tumor histology's type of related measurement and tumor resection, classification and make by stages.This analysis will be for example comprising next From the tumour of the patient (women and male) between 18 to 80 years old.(seldom seeing thyroid cancer in the patient less than 18 years old). Alternatively, tumour can be with narrower age bracket feature or individually for masculinity and femininity, with based on age or sex Identification difference.It can be analyzed across ethnic group or race or individually for ethnic group or race, such as, to identify whether to deposit In the difference based on ethnic group or race.For the number of dominated variable, the serious disease (example with non-cancer can be excluded Such as, hypertension, diabetes and bleeding problems) object.

In order to construct in the database for making tumor information related to FNE data, database comprising the trouble for being taken out tumour Person identification information (for example, age, sex, ethnic group or race) and tumor information (for example, by stages, classification, AFM measurement and FNE is measured).For privacy concern, each tumour is recognized with numeral rather than with patient name.

Clinically applicable agreement can be used in obtaining and handle thyroid cancer tissue for analysis.For example, can be Flesh tissue sample is measured in obtain sample 1 to 2 hour.(for example, drawing in ultrasound during in pin insertion tumour Lead down) power and pin puncture depth, 25 FNE measurements can be recorded for each tissue samples.Magnetic can be used to pass Sensor controls position, paracentesis depth and the anglec of rotation of pin to carry out 3D mappings.Data can be stored in safe computing device On for further analysis.The Young's modulus of sample can be obtained based on puncture distance of the pin in tissue, and can be based on Pin being differently directed in interest region produces the 3D mappings of organization mechanicses.Can be based on the biomethanics in interest region Pattern writes down sample (for example, as shown in Table 4).In order to which data are fitted, peakology function can be used to position peak value, And multimodal fitting can be applied to Stiffness Distribution.Data are able to record that as the average value with standard deviation.It can use and match somebody with somebody (P≤0.05) is examined to assess the poor statistical significance in average value student t.

For comparative purposes, can be for each parathyroid tissue sample according to five work of assessment of standard pathological process Inspection.For example, after ablation, a biopsy can be immediately available for AFM analyses.

After FNE, (retrieved), formaldehyde can be fetched again according to Standard histological process and fixed and paraffin bag Bury all five biopsy samples.The section with about 5 μ m thicks can be cut, and the section is transferred to coated glass and is carried On piece.The first slide glass and last slide glass in serial section can be dyed with h and E (H＆E) coloring agent.Subsequently Histopathological examination, which can be included, to be assessed lesion type (for example, according to table 4) and determines standard histopathologic marker The number of (for example, degree of tumor-infiltrated, fibrosis, necrosis and lymphocytic infiltration).

Biopsy samples can be immediately transferred to the ice-cold isobaric Ringer's solution supplemented with glucose and protease inhibitors, and 4 DEG C are maintained to minimize tissue degradation.Each sample can be fixed on the vinyl disc with epoxy glue thin layer.Can be 37 AFM (for example, using the catalyst AFM being arranged on inverted light microscope) is performed at DEG C.It is able to record that 24 × 24 dot grids Up to 22 different 20 × 20 μm on (pixel sizes of every 576 force-displacement curves of mapping graph and 833nm)²Power-body Product (F-v) mapping graph.500 μm spaced apart of F-v mapping graphs can be systematically obtained across sample surface.Maximum applies load force 1.0nN can be configured to, wherein the intrinsic mechanics that about 150nm to 3000nm depth of cup is depended in each biopsy is poor It is different.Hertz-Sneddon model analysis force curves can be used.The rigidity calculated according to force curve can spatially be drawn Value (KPa) is to produce the rigidity mapping graph (for example, using Mathworks MATLAB) of color coding.Can be in FNE Biological Strengths / inhomogeneities distribution, AFM organize stiffness measurement and oncological pathology by stages and perform correlation analysis between classification.

The database created by described technology can be used in assessing the difference of thyroid cancer (or other scramblings) Overall coherence between Histopathology.

The described technology for being used to create database is presented and not restricted by way of example.It can perform Extra test, thus it is possible to vary test condition, by increasing capacitance it is possible to increase for the FNE measurements measured and the number of directional angle, can obtain Extra correlation etc..

Example 4

FNE devices for the in-vivo measurement of breast tissue

FNAB (fine needle aspiration biopsy) has been used for diagnosis and examination, because FNAB is for the fast of minimally invasive breast lesion assessment Speed and with cost-benefit technology.However, more invasive core biopsies have largely replaced the base of breast cancer In FNAB diagnosis, because the deciphering of FNAB samples lacks architecture mode, and FNAB is needed by experienced cell pathology Family assesses, and cannot distinguish between carcinoma in situ and infiltrating cancer.Another technology, i.e. elastograph imaging method by the elastic characteristic of tissue into Picture, and have been used for determining the relation between different structure and its tissue elasticity in recent years, this can aid in Diagnosis of malignant and swells Knurl.Healthy breast tissue is the main uneven texture being made up of fat and gland tissue with different elastic characteristics, and There is modulus of elasticity (rigidity) between normal galactophore tissue and tumour poor.Pernicious change is related to organizing the change of rigidity, from And cause stone modulus.For example, research shows compared with normal galactophore tissue, due to associated rush connective tissue proliferation Property reaction, surrounding tissue infiltration and intubation intervention, up to 15 times of the Young's modulus increase of invasive ductal carcinoma.By comparing, Papillomatous rigidity is about five times of normal structure.Rigidity imaging based on elastogram can provide extra compared with hand is touched Improved sensitiveness, objectivity or details, for example, stiffness mode；However, elastogram expensive (for example, higher than $ 200K), fixed Property and need special instrument instrument and operating technology.In addition, breast elasticity imaging is due to breast tissue and the configuration aspects of tubercle And injured depth and with limitation, and need operator's experience to obtain repeatable result.Therefore, still suffer to it is quantitative, The unmet demand of cost efficient and wieldy early-stage breast cancer diagnostic techniques.

, can be with Diagnosis of Breast cancer, because tumour is harder than surrounding tissue and malignant tumour by measuring in-vivo tissue rigidity Than benign tumour much harder (also, abnormally, malignant cell is much softer than normal cell).

Actin cytoskeleton it is determined that cell mechanical characteristic when it is extremely important.Found using AFM, the chest with patient The transfer cell softer than normal cell 70% of chamber hydrops isolation, so as to show that transfer can be by cell compliance (cell Compliance) promote.Under macroscopic scale, thus the acicular constituent resistance to deformation around cancer feels hard when palpation.Cause This, tissue elasticity will be different depending on measurement scale.Anisotropy and nonlinear biological tissue elasticity will depend on deformation Direction and degree and it is different.The force-responsive of whole tumour by the rigid structure element (for example, collagen) in surrounding matrix, Increased apposition and the crosslinking during growth of cancers are occupied an leading position.Normal gland tissue, benign lesion and pernicious Tumour qualitatively shows unique biomethanics mark, so that reproducible between different patients.Malignant tumour, which shows, meets group Knit the mechanical heterogeneity for learning outward appearance, and the spy in the region of the tumour cell with tight clusters and less intermediary's matrix Property relatively low stiffness peak value.On the other hand, normal galandular epithelium and benign real venereal disease, which become, shows unimodal (unimodal) but different Stiffness Distribution.Breast cancer tissue shows the modulus of elasticity (Young's modulus) higher than normal glandular tissue.On the whole, it is evident that It is that nanometer dynamic performance analysis provides determining for the clinical diagnosis of the palpable cancer (for example, breast cancer) with conversion meaning Figureofmerit.

The mechanical meaurement according to cancer cell and the result of tissue demonstration are mapped using extensive power, is examined with improving breast cancer Disconnected sensitiveness.

The relation between tumour hardness and cytodiagnosis is have studied in initial clinical research.By using hypodermic injection Pin is detected and the rigidity that runs into of detection pin manually, and the internal rigidity test based on reality thyroid tumors is by thyroid tumors (609 therein) are divided into tumprigenicity or Non-cancerous.Then, rigidity ranking is related to final cell diagnosis.Realize 0.81 Cancer detection sensitiveness and 0.89 specificity.However, the major limitation of this technology include according to the resistance of pin puncture come Qualitative evaluation thyroid nodule rigidity, this is easily influenceed by operator's prejudice and shortage quality control.The FNE devices of the disclosure (for example, FNE devices 110,410 and 1310) provides the improvement Sensitivity and Specificity with qualitative assessment.

FNE technologies described in the disclosure further provide for being used to determine irregular cancer beside organism.For example, finding mammary gland The cancer beside organism of tumour is still challenging.For example, early-stage breast cancer treatment in, by mammogram, ultrasonic wave or MRI positioning tumors in the preoperative；Then, during operation (lumpectomy), tumor resection agglomerate and normal structure Buffer solution, to avoid the necessity of subsequent procedures.Some researchs are it has been determined that cancer beside organism's state is to predict local recurrence most One of key factor.In order to verify the buffer solution for having obtained normal structure, in surgical procedure, inking and assessment are cut on pathology Except tissue so that cancer beside organism is evaluated as into positive (cancer cell at inked surface/closely inked surface), close to (cancer cell In about 1-2mm) or it is negative (cancer cell is farther, typically larger than 1-2mm).However, for obtaining the cancer beside organism of operation enough Pathology evaluation in art, for example, the frozen section analysis (FSA) of mammary fat tissue is challenging.In addition to FSA, Test other technique successful rates and assess cancer beside organism with differing, include intraoperative ultrasound ripple and cytology of impression slide (IC).However, due to Technology and other limitations, are often used without these technologies (for example, referring to table 5, presenting and choosing when detecting tumour cancer beside organism interface War).

Table 5

Therefore, there is still a need for more preferably in preoperative and art the combination of method to supplement pathology evaluation to obtain enough hands Art cancer beside organism.FNE is minimally invasive, and can be used in the preoperative or in art based on the power between health tissues and cancerous tissue Characteristic (Young's modulus) difference is learned to assess the breast lesion of palpable or breast x lines irradiation.

In this example 4, prototype FNE devices and the 3D biomethanics mapping for doubtful mammary gland cancerous node and Young's modulus And the FNA breast biopsy pins of the analysis of micron order tubercle rigidity inhomogeneities are integrated.The design of example 4, which is included, has quantitative power The user interface of data display equipment is learned, for assessing in real time, documenting and doing decision-making.

FNE devices are included senses No. 25 gauge FNA pins that piezoelectric solid cylinder is installed to hand-held tool by power.Electric charge Amplifier produces the voltage proportional to insertion force.This voltage and data from position sensor are collected simultaneously by microprocessor And computing device is sent to, the computing device provides data processing, data display, data storage and communication.Due to data Privately owned essence, computing device can be that safe and data storage device can be safe.

Power sensing piezoelectric solid cylinder includes piezoelectric, and the piezoelectric shows the electric charge position in response to pressure applied Move.Charge amplifier produces the voltage output of the proportional pressure with being applied to piezoelectric solid cylinder so that the voltage output is The measured value of insertion force on FNA pins.FNE devices piezo tube measures axial insertion force, and being divided into makes device to measure The quadrant of laterally inserted power.This provides the immediate feedback that angle is inserted on pin to operator, and provides software for pin position Correction (for example, due to insertion angle, or the pin position caused by being bent by pin changes).

Use the pin position of the FNE devices of resistor coding device (potentiometer) Mapping Examples 4.Many low cost microcontroller tools There is the airborne ADC that can be used in digitizing potentiometer value.Linear potentiometer with 4cm strokes can be digitized to 10 precision To realize 40 μm of positioning precision, this diffraction limit than ultrasonic wave, MRI or CT is fine about 10 times.

Ultrasonic wave is sensed for position.Alternatively, the 6 axle gyroscopes with 3 axle accelerometers can be used for position sensing, or Position sensing can the change based on the secondary harmonics of pin, this depend on organization internal pin length.

Figure 16 illustrates the mapping of the internal tumor of breast of the FNE devices using example 4.As illustrated, the pin of FNE devices exists Inserted at pin insertion point, then with different (3D) angles and depth movement with according on the pin such as detected by force snesor Power maps tumour.

Different histological type of breast benign based on tumour inhomogeneities and biomethanics and database by stages are to be based on Multiple doubtful Breast Nodules samples from the patient for being subjected to part or all of breast excision operation.Database can be used in checking FNE diagnostic sensitivities and specificity and it is related to histopathology.Measurement agreement describes to be used for external FNE and AFM, includes reality Apply blind Journal of Sex Research.For database, FNE is used to analyze the excision mammary gland knot from 60 female patients between 18 years old and 80 years old Section, and make power measurement and Young's modulus (AFM) and tumor histology's type, be classified and by stages related.Patient is excluded with non- The serious disease (for example, the hypertension not controlled, the diabetes not controlled and severe haemorrhage imbalance) of cancer Object.The technology of data for collecting database is described relative to example 3.

In addition, by the FNE data in all six cancer beside organisms's (upper and lower, middle, transverse direction, front and rear) of resection organization With macropathology assessment compared with determine predict clear cancer beside organism when FNE measurement sensitiveness.

Terminate comment

Therefore, described in the disclosure the device for the minimally invasive internal FNE biopsies based on power inhomogeneities, system and Technology.Advantage comprising reduce instrument size, reduce system cost, quick diagnosis and in the environment of resource shortage (for example, Unavailable ultrasonic instrument, or lack qualified FNAC virologist) diagnosis.In addition, FNE devices, system and technology provide use In auxiliary diagnostic tool.On cancer parietal cell (for example, in lumpectomy or other operations), FNE devices, system and Technology can be used in limiting in surgical procedure excision cancer parietal cell (for example, rather than carry out multiple frozen section examination, it is described Frozen section examination can be very inaccurate, time-consuming (often cutting into slices at least 15 minutes) and need pathology and histology to support).

FNE devices described in the disclosure may be embodied as the annex of another device (such as cell taking gun).Embodiment party herein In case, FNE devices can be comprising sensor and for the wired or wireless communication interface in PERCOM peripheral communication.For example, with reference to Fig. 1, FNE devices 110 can include detecting element 120 as described, force snesor 130 and outer cover unit 140, and can enter one Step provides the communication interface to external device (ED) (for example, computing device) comprising the data for being used to receive from force snesor 130.

Singular references " one " used herein, " one " and " (the) " include a plurality of signified things, unless up and down Text is clearly dictated otherwise.Thus, for example, multiple objects can be included to referring to for object, unless context is expressly otherwise Indicate.

Terms used herein " substantially ", " substantially " and " about " is used to describe and consider small change.When combining thing Part or situation in use, the term can the example that accurately occurs of self-explanatory characters' part or situation and event or situation closely send out Raw example.For example, the term can refer to less than or equal to ± 10%, for example, being less than or equal to ± 5%, being less than or equal to ± 4%, less than or equal to ± 3%, less than or equal to ± 2%, less than or equal to ± 1%, less than or equal to ± 0.5%, be less than Or equal to ± 0.1%, or less than or equal to ± 0.05%.

Terms used herein " connection, connection, connector " refer to operation coupling or connection.The object of connection can It is directly coupled to another one or for example can be indirectly coupled to another one via another collection of objects.

Terms used herein " size " refers to the characteristic size of object.Thus, for example, spherical object be sized to refer to The diameter of object.In the case of the object of aspherical, the diameter for being sized to refer to correspondence spherical object of non-spherical object, its In corresponding spherical object show or with substantially with non-spherical object obtain or measurable characteristic identical can be obtained Or the specific collection of measurable characteristic.When the collection of object is collectively referred to as with particular size, it is contemplated that object can have in spy Determine the size distribution around size.Therefore, the typical case that " size of collection of objects " used herein can refer in size distribution is big It is small, for example, mean size, middle size or peak value size.

Although the disclosure is described with reference to the specific embodiment of the disclosure, although it will be understood by those skilled in the art that not Depart from the case of the true spirit and scope of the disclosure as defined by the appended claims can with various changes can be made simultaneously And can be replaced with equivalent.Furthermore it is possible to many modifications may be made so that particular case, material, the composition of material, method, one or Multiple operations are adapted to target, the spirit and scope of the disclosure.All such modifications are directed at the model of appended claims In enclosing.Specifically, although some methods may be described with reference to the specific operation performed by particular order, however, it is understood that These operations can combine, segment or resequence to form equivalent method in the case where not departing from the teaching of the disclosure.Cause This, unless explicitly pointed out herein, the order otherwise operated and packet are not limitations of this disclosure.

Claims (21)

1. a kind of elastogram system, it includes：

Hand-held elastogram device, it is included：

Shell；

Detecting element, it is detachably attached to the shell；And

Force snesor, it is attached in the shell, and the force snesor is connected to the detecting element；And

Position sensing apparatus, it is connected to the elastogram device.

2. elastogram system according to claim 1, wherein the detecting element is pin, pipe or line.

3. elastogram system according to any one of claim 1 to 2, wherein the force snesor be piezo-electric crystal, Strain gauge or displacement transducer.

4. elastogram system according to any one of claim 1 to 3, wherein the position sensing apparatus is coding Level.

5. elastogram system according to any one of claim 1 to 3, wherein the position sensing apparatus is ultrasonic position Displacement sensor, magnetic displacement transducer or electric displacement sensor.

6. elastogram system according to any one of claim 1 to 5, wherein force snesor are configured to produce instruction The signal of the power of the detecting element is applied in the detecting element insertion material, and the elastogram system enters one Step includes being connected to the processing unit of the force snesor, wherein the processing unit is configured to obtain institute based on the signal State the mapping of the spatial variations of material property in material.

7. elastogram system according to claim 6, wherein the material is biological tissue, and the processing unit It is configured to obtain the instruction of the possibility of the scrambling of the biological tissue based on the mapping.

8. elastogram system according to claim 6, wherein the material is biological tissue, and the processing unit It is configured to obtain the instruction of the possibility of cancer based on the mapping.

9. elastogram system according to claim 6, wherein the material is biological tissue, and the processing unit It is configured to the classification based on the mapping acquisition cancer or instruction by stages.

10. elastogram system according to any one of claim 1 to 9, wherein the detecting element is FNA One in pin or fine-needle aspiration biopsy pin, the FNA pin is FNA pins, and the fine-needle aspiration biopsy pin is FNB pins.

11. a kind of hand-held elastogram system, it includes：

Shell；

Pin, it is detachably attached to the shell；And

Force snesor, it is located in the shell and is fixedly mounted relative to the pin, and the force snesor is configured to inspection Survey the power for being applied to the pin.

12. elastogram system according to claim 11, it further comprises the microprocessor being located in the shell, The microprocessor is configured to obtain the parameter for the power for representing to be detected at the force snesor.

13. the elastogram system according to any one of claim 11 to 12, wherein the force snesor is piezoelectricity dress Put, it further comprises：

Charge amplifier, it is couple to the force snesor to detect stored charge, and the charge amplifier is further coupled to The microprocessor and output voltage, the voltage are the ginsengs of the power for representing to detect at the force snesor Number.

14. the elastogram system according to any one of claim 11 to 13, it further comprises：

Serial line interface, it is couple to the microprocessor and is configured to communicate with the device of the housing exterior.

15. elastogram system according to claim 11, it further comprises the processing for being connected to the force snesor Unit, wherein the processing unit is configured to obtain in material based on the power detected at the force snesor The mapping of the spatial variations of material property.

16. the elastogram system according to any one of claim 11 to 15, wherein the pin is FNA pin, institute State FNA pin i.e. FNA pins.

17. the elastogram system according to any one of claim 11 to 16, wherein the force snesor is configured to Detection is applied to the axial force and cross force of the pin.

18. elastogram system according to claim 11, it further comprises microprocessor and is attached to the shell Position sensing apparatus, wherein the microprocessor is couple to the position sensing apparatus and is configured to be based on from described The information of position sensing apparatus and the path for adjusting the pin.

19. a kind of elastograph imaging method, it includes：

By in detecting element insertion material；

Produced by the force snesor for the base for being connected to the detecting element and indicate to be applied to the detection member by the material The signal of the power of part；And

Based on the signal, the mapping of the spatial variations of material property in the material is obtained.

20. elastograph imaging method according to claim 19, wherein the material is biological tissue, and methods described is entered One step includes, and based on the mapping, obtains the instruction of the possibility of the scrambling of the biological tissue.

21. elastograph imaging method according to claim 19, wherein the spatial variations indicate the uneven of the material Property.